The Nutritional Cytokine Leptin Promotes NSCLC by Activating the PI3KAKT and MAPKERK Pathways in NSCLC Cells in a Paracrine Manner
Joint Authors
Li, Fengzhou
Zhao, Shilei
Guo, Tao
Li, Jinxiu
Gu, Chundong
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-18
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Purpose.
Leptin is a nutritional cytokine encoded by the obesity gene whose concentration in the tumor microenvironment is closely related to the occurrence and progression of cancer.
However, previous evidence has suggested that there is no clear relationship between serum leptin concentrations and lung cancer progression.
Cancer-associated fibroblasts (CAFs), the most abundant component of the tumor microenvironment in a variety of solid tumors, were recently reported to produce leptin.
Therefore, it was inferred that leptin is most likely to affect non-small-cell lung cancer (NSCLC) through an autocrine and paracrine mechanism.
In the current study, we investigated the paracrine effect and mechanism of leptin produced by CAFs on NSCLC by establishing a novel in vitro cell coculture system.
Methods.
A noncontact coculture device was designed and made by 3D printing.
CAFs and paired normal lung fibroblasts (NLFs) from 5 patients were successfully isolated and cocultured with two NSCLC cell lines in a coculture system.
The background expression of leptin was detected by western blot.
The in situ expression of leptin and its receptor (Ob-R) in NSCLC tissues and paired normal lung tissues was analyzed by immunohistochemistry.
Furthermore, we downregulated the expression of leptin in CAFs and assessed changes in its promotion on NSCLC cells in the coculture system.
Finally, changes in the phosphorylation of ERK1/2 and AKT were examined to investigate the molecular mechanisms responsible for the paracrine promotion of NSCLC cells by leptin.
Results.
Leptin was overexpressed in nearly all five primary CAF lines compared with its expression in paired NLFs.
IHC staining showed that the expression of leptin was high in NSCLC cells, slightly lower in CAF, and negative in normal lung tissue.
Ob-R was strongly expressed in NSCLC cells.
The ability of A549 and H1299 cells to proliferate and migrate was enhanced by high leptin levels in both the cocultured fibroblasts and the culture medium.
Furthermore, western blot assays suggested that the MAPK/ERK1/2 and PI3K/AKT signaling pathways were activated by leptin produced by CAFs, which demonstrated that the functions of paracrine leptin in NSCLC are as those of the serum leptin to other cancers.
Conclusion.
Leptin produced by CAF promotes proliferation and migration of NSCLC cells probably via PI3K/AKT and MAPK/ERK1/2 signaling pathways in a paracrine manner.
American Psychological Association (APA)
Li, Fengzhou& Zhao, Shilei& Guo, Tao& Li, Jinxiu& Gu, Chundong. 2019. The Nutritional Cytokine Leptin Promotes NSCLC by Activating the PI3KAKT and MAPKERK Pathways in NSCLC Cells in a Paracrine Manner. BioMed Research International،Vol. 2019, no. 2019, pp.1-8.
https://search.emarefa.net/detail/BIM-1123940
Modern Language Association (MLA)
Li, Fengzhou…[et al.]. The Nutritional Cytokine Leptin Promotes NSCLC by Activating the PI3KAKT and MAPKERK Pathways in NSCLC Cells in a Paracrine Manner. BioMed Research International No. 2019 (2019), pp.1-8.
https://search.emarefa.net/detail/BIM-1123940
American Medical Association (AMA)
Li, Fengzhou& Zhao, Shilei& Guo, Tao& Li, Jinxiu& Gu, Chundong. The Nutritional Cytokine Leptin Promotes NSCLC by Activating the PI3KAKT and MAPKERK Pathways in NSCLC Cells in a Paracrine Manner. BioMed Research International. 2019. Vol. 2019, no. 2019, pp.1-8.
https://search.emarefa.net/detail/BIM-1123940
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1123940